Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways

Abstract

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.

Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data

“…The process of aging involves most (if not all) aspects of life and in molecular terms, it thus involves a wide variety of signaling pathways at least to some degree. Aging is considered to be the causal process underlying age-associated disease and dysfunction (Fuellen et al, 2019). Accordingly, increasing chronological age is the foremost risk factor for the development of all kinds of chronic diseases such as type 2 diabetes, cardiovascular disease, osteoporosis, arthritis, Alzheimer’s disease and cancer, along with age-associated dysfunction such as frailty and sarcopenia.…”

A proteomic signature of healthspan

“…Unlike lifespan, which has a universal definition, there is no consensus on the definition of healthspan 5,6 . Previous research has suggested characterizing healthy aging in five domains: physical capability, cognitive function, physiological and musculoskeletal, endocrine, and immune functions 5,7 .…”

Identification of healthspan-promoting genes in Caenorhabditis elegans based on a human GWAS study

“…However, the continuous increase in life expectancy, paired with an unchanged age of the onset of morbidity and ageing-associated diseases (Crimmins 2015) highlights that lifespan is not representative for the various phenotypes of ageing. Thus, the focus is increasingly on health and healthspan, defined by the lack of diseases and dysfunctions addressing physiological, physical, cognitive, and reproductive functions (Fuellen et al 2019).…”